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Cell Host Microbe. 2016 Mar 9;19(3):323-35. doi: 10.1016/j.chom.2016.02.010.

SIV Infection-Mediated Changes in Gastrointestinal Bacterial Microbiome and Virome Are Associated with Immunodeficiency and Prevented by Vaccination.

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: shandley@pathology.wustl.edu.
2
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
3
Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
4
Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
5
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and Harvard, Boston, MA 02114, USA.
6
Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
7
Section of Anatomic Pathology, Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
8
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
9
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: virgin@wustl.edu.

Abstract

AIDS caused by simian immunodeficiency virus (SIV) infection is associated with gastrointestinal disease, systemic immune activation, and, in cross-sectional studies, changes in the enteric virome. Here we performed a longitudinal study of a vaccine cohort to define the natural history of changes in the fecal metagenome in SIV-infected monkeys. Matched rhesus macaques were either uninfected or intrarectally challenged with SIV, with a subset receiving the Ad26 vaccine, an adenovirus vector expressing the viral Env/Gag/Pol antigens. Progression of SIV infection to AIDS was associated with increased detection of potentially pathogenic viruses and bacterial enteropathogens. Specifically, adenoviruses were associated with an increased incidence of gastrointestinal disease and AIDS-related mortality. Viral and bacterial enteropathogens were largely absent from animals protected by the vaccine. These data suggest that the SIV-associated gastrointestinal disease is associated with the presence of both viral and bacterial enteropathogens and that protection against SIV infection by vaccination prevents enteropathogen emergence.

KEYWORDS:

AIDS; SIV; adenovirus; circovirus; microbiome; picornavirus; vaccine; virome

PMID:
26962943
PMCID:
PMC4802495
DOI:
10.1016/j.chom.2016.02.010
[Indexed for MEDLINE]
Free PMC Article

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